Status: FDA approval withdrawn in 2006

Organizations involved:

Massachusetts Biol. Labs. – Manuf.; R&D; Tech.

Massachusetts, State of – Parent

FFF Enterprises, Inc. – USA mark.

Cross ref: See the entry for Varicella Virus Vaccine Live (Oka/Merck) or Varivax entry (#564) for background information on varicella virus. See the entry below for VariZIG, which is available in the U.S. to replace this product. See the Immune Globulin Products entry (#743).

Description: Varicella-Zoster Immune Globulin (Human) or VZVIG is an aqueous formulation of immune globulin containing high titers of varicella-zoster virus (VZV; chickenpox; herpes zoster) antibodies obtained from fractionated pooled Plasma from donors with high titers of varicella-zoster virus antibodies (having received VZV vaccination with Varivax from Merck & Co.). This is the only immune globulin or biopharmaceutical product approved for treatment of a herpesvirus infection (VZV), but is no longer manufactured. Unlike its current U.S. replacement (see entry below), which is injected intramuscularly, this VZVIG is administered by intravenous injection.

Nomenclature: Varicella-Zoster Immune Globulin/Mass. [BIO]; Varicella-Zoster Immune Globulin (Human) [FDA]; Varicella-Zoster Immune Globulin USP [USP]; VZVIG [SY]

Companies.: VZVIG was developed and manufactured by the Massachusetts Biological Labs., CBER/FDA lic. no. 0064. manufacture was halted in Feb. 2005. FFF Enterprises, Inc. exclusively marketed VZVIG in the U.S.

Manufacture: VZVIG is manufactured much the same as other immune globulins (see #743), using pooled plasma from persons having received VZV vaccine (Varivax). In June 2002, the Marketing Research Bureau reported that the average price paid by plasma fractionators for purchase of plasma with high titer of VZV antibodies was $135-$140/L.

FDA class: Biologic PLA

CBER class: Blood And Blood Derivatives

Approvals: Date = 19801223; first approval. PLA

Indications: for post-exposure prophylaxis, particularly in persons receiving cancer chemotherapy, those with compromised immunity, and those lacking preexisting immunity to VZV [unofficial]

Status: VZVIG approval is still valid, and the product is still be available for those needing it, while supplies last. However, this product is rarely used. In early 2006, supplies were nearly exhausted.

In Feb. 2005, the Massachusetts Biological Labs. announced its was permanently discontinuing manufacture of VZVIG. A replacement product (see the VariZIG entry below) recently became available in the U.S. under IND. The approval was subsequently voluntarily withdrawn.

On May 2, 2006, MPHBL discontinued manufacture of VZIG. A limited supply of VZIG remains (2013). Investigational (not licensed) VZIG product is available under an investigational new drug application (IND) protocol from FFF Enterprises.

Disease: See the entry (#564) for Varicella Virus Vaccine Live (Oka/Merck) or Varivax entry for further information about the virus and disease.

Medical: Although generally encountered as a pediatric disease, VZV infection can be deadly and VZVIG can be lifesaving, particularly in at-risk persons lacking immunity. Most persons gain immunity to VZV from contracting chickenpox as a child, with resulting immunity lasting decades. Anti-herpesvirus drugs, such as valacyclovir (Valtrex) from GlaxoSmith-Kline and famciclovir (Famvir) from Novartis, are now primarily used for treatment and prophylaxis against disease due to varicella-zoster virus infection. These drugs are generally highly effective.

VZVIG is used to provide passive immunization for VZV-exposed, susceptible individuals at risk of complications from varicella (chickenpox). The Advisory Committee for Immunization Practices (ACIP), Centers for Disease Control and Prevention (CDC) recommends VZVIG use in immunocompromised patients; neonates whose mothers have signs and symptoms of varicella around the time of delivery (i.e., 5 days before to 2 days after); premature infants born at >28 weeks of gestation who are exposed during the neonatal period and whose mothers do not have evidence of immunity; premature infants born at <28 weeks of gestation or who weigh <1,000 g at birth and were exposed during the neonatal period, regardless of maternal history of varicella disease or vaccination; and all pregnant women. Varicella vaccine (see Varivax entry) was recommended in 1999 for postexposure prophylaxis of other persons without evidence of varicella immunity and who have no contraindications: to vaccination. VZVIG provides maximum benefit when administered as soon as possible after exposure, although it can be effective if administered as late as 96 hours after exposure; treatment after 96 hours is of uncertain value. For pregnant women who cannot receive VZVIG within 96 hours of exposure, clinicians may choose either to administer IGIV or closely monitor the women for signs and symptoms of varicella and institute treatment with acyclovir, valacyclovir or famciclovir if illness occurs.

The timing of VZVIG administration after varicella (chickenpox) or herpes zoster (recurrence of VZV infection in older persons having lost immunity from childhood infection) exposure is critical. Treatment is most effective when it is begun within 96 hours after virus exposure; while treatment after 96 hours is of uncertain value. Because of the time limitation, many major clinical centers keep a small supply of VZVIG on hand.

Any patient who receives VZVIG should be observed closely for signs or symptoms of varicella for 28 days after exposure because VZVIG might prolong the incubation period by >1 week. Antiviral therapy, e.g., acyclovir or famciclovir, should be instituted immediately if signs or symptoms of varicella disease occur.

Market: The 2005 Average Wholesale Price (AWP) is $153.42/1.25 mL, 125 U vial, and $754.73/6.25 mL, 625 U vial (Red Book, 2005). These prices were unchanged from 2004.

In its March 22, 2006, price list, FFF Enterprises, a major biologics distributor, reported its prices as $122.73/125 units vial; and $603.78/625 units vial (same in 2005 and 2004).